Vancomycin is a known antimicrobial which can be used clinically in aqueous solutions for intravenous or oral administration and in peritoneal dialysis fluids. It is particularly effective against Staphylococcus and is therefore employed to combat staphylococcal infections which are resistant to penicillin. See Geraci and Hermans (1983), Mayo Clin. Proc. 58: 88-91. It is administered intravenously for treatment of systemic infections. Its oral use is primarily for staphylococcal ileocolitis and antibiotic-induced enterocolitis associated with Clostridium difficile. It has also been shown to be useable in peritoneal dialysate solutions. See Sewell and Golper (1982), Antimicrobial Agents and Chemotherapy 21 (3): 528-529.
Vancomycin may be produced by the process described in U.S. Pat. No. 3,067,099. It is available commercially from Eli Lilly & Company, Indianapolis, Ind. under the product name "Vancocin". It is commonly marketed and used in salt form, that is, as vancomycin hydrochloride.
The structures of vancomycin and other vancomycin-type antibiotics have been widely studied. The definitive structure of vancomycin is believed to be shown in two recent publications: Williamson and Williams (1981), J. Am. Chem. Soc. 103: 6580-6585; and Harris and Harris (1982), J. Am. Chem. Soc. 104: 4293-4295. The structure is a linear heptapeptide containing an actinoidinic acid and a vancomycinic acid. As reported in the latter reference, the structure of vancomycin includes an asparagine residue which is subject to rearrangement. The mechanism of this rearrangement has been investigated (Harris, Kopecka and Harris (1983), J. Am. Chem. Soc. 105:6915-6922). The rearrangement product lacks antibiotic activity (Marshall (1965), J. Med. Chem. 8: 18-22).
The preferred clinical practice is to use the vancomycin solution within 24 hours after preparation. However, it is known that aqueous solutions of vancomycin can be stored for several weeks at refrigeration temperatures (viz. 5.degree. C.), but that potency is lost and autogenous pH changes occur either at room temperature or after prolonged storage under refrigeration. See Mann, Coleman,, and Boylan (1971), Am. J. Hosp. Pharm. 28: 760-763; and Wamberg, Nielsen, and Scheibel (1979), Arch. Pharm. Chem. Sci. Ed. 8: 1-4.
It is known that vancomycin-type antibiotics form a complex in aqueous solution, particularly with peptides terminating in D-alanyl-D-alanine. The classes of dipeptides and tripeptides binding in aqueous solution to vancomycin and other vancomycin type antibiotics are known. See Nieto and Perkins (1971), Biochem. J. 123: 789-803; and Perkins (1982), Pharmac. Ther. 16: 181-197.